Expanded nk cell fractions for transplantation in combination therapy

a technology of nk cell and combination therapy, which is applied in the field of hematological disease treatment methods, can solve the problems of poor in vivo function, limited experimental protocol date, and unrealized full therapeutic potential of nk cell-based immunotherapy

a technology of nk cell and combination therapy, which is applied in the field of hematological disease treatment methods, can solve the problems of poor in vivo function, limited experimental protocol date, and unrealized full therapeutic potential of nk cell-based immunotherapy

US20220249555A1Pending Publication Date: 2022-08-11GAMIDA CELL
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  • Expanded nk cell fractions for transplantation in combination therapy
  • Expanded nk cell fractions for transplantation in combination therapy

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examples

[0322]Reference is now made to the following examples, which together with the above descriptions, illustrate some embodiments of the invention in a non-limiting fashion.

[0323]Generally, the nomenclature used herein and the laboratory procedures utilized in the present invention include molecular, biochemical, microbiological and recombinant DNA techniques. Such techniques are thoroughly explained in the literature. See, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988); Watson et al., “Recombinant DNA”, Scientific American Books, New York; Birren et al. (eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, Cold Spring Harbor Laboratory Press, New York (1998); methodologies as se...

example i

ide Enhances Fc Receptor (CD16) Expression on NK Cells

[0333]Recognition of antibody coated cells by NK cell-surface Fc receptors (FCgammaRIII), also known as CD16, leads to direct cell killing and cytokine production by peripheral blood NK cells. FACS analysis of surface CD16 expression in NK cells cultured with added exogenous nicotinamide (5 mM) indicates abundant expression of CD16 in the CD3- / CD56+NK cell population (see FIG. 1—CD56+ / CD16+ fraction=>75%).

example ii

Antibody Dependent Cellular Cytotoxicity (ADCC) in NK Cells Expanded with Nicotinamide

[0334]CD20 is a B-cell tumor surface marker of increasing clinical significance for immunotherapy of hematological cancers (e.g. lymphomas and leukemias) and B-cell autoimmune diseases. A number of CD20-targeted monoclonal antibodies have been approved for clinical use.

[0335]The present inventors have previously shown (see PCT Publication WO 2011 / 080740) that culture with added exogenous nicotinamide enhances NK cell proliferation in culture, enhances NK cell motility, and enhances migratory (CXCR4), adhesion (CD49e) and trafficking (CD62L) receptor expression in cultured cord-blood derives NK cells.

[0336]In order to evaluate the efficacy of CD20-mediated “cell killing” function of nicotinamide-expanded NK cells, NK cells expanded with nicotinamide were incubated with BL2 (Burkitt's Lymphoma cells, CD20+) and anti-CD20 monoclonal antibodies Rituximab and obinutuzumab in an ADCC assay.

[0337]While bo...

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Abstract

Methods of expanding a natural killer (NK) cell fraction for transplantation into a subject are provided, and particularly, methods for providing transplantable NK cell fractions and protocols for their use, which can be employed for applications in cell transplants and infusions, in particular, in combination therapy with anti-CD20 anti-cancer antibodies for treatment of cancer and other disease.

Description

RELATED APPLICATION / S[0001]This application claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 821,535 filed on 21 Mar. 2019, the contents of which are incorporated herein by reference in their entirety.FIELD AND BACKGROUND OF THE INVENTION[0002]The present invention relates to methods of expanding natural killer (NK) cells, selection of expanded NK cell populations for transplantation to subjects in need thereof and the therapeutic use of suitable, ex-vivo expanded NK cell fractions for transplantation in the clinical setting, for treatment of hematological malignancies, including in combination with cancer immunotherapy. The present invention also envisions kits comprising the expanded NK cell fractions.[0003]Natural killer (hereinafter also abbreviated as “NK”) cells are lymphoid cells that participate in immune reactions. These cells have a variety of functions, especially the killing of tumor cells, cells undergoing oncogenic transformation and other a...

Claims

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Application Information

Patent Timeline
11 Aug 2022
Publication
US20220249555A1
IPC
A61K35/17; A61P35/02; A61K39/395; A61K31/675; A61K31/7076; C12N5/0783; A61K38/20
CPC
A61K35/17; A61P35/02; A61K39/39558; A61K31/675; A61K2039/545; C12N5/0646; A61K38/2013; C12N2501/2315
Inventors
PELED, TONY